Posts tagged ‘Immune Checkpoint Inhibitors’

In a landmark publication today, the prestigious journal Nature includes five “Letters” regarding checkpoint blockade of the programmed death-1 (PD-1) receptor and its ligand PD-L1. It confirms the promise and potential of the emerging field of immuno-oncology to provide durable and long lasting responses in many cancers.

“There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years.”

On the basis of this data, MPDL3280A received Breaththrough Therapy Designation from the FDA earlier this year.

Roy Herbst (Yale) and colleagues in their Nature Letter write about biomakers of PD-L1 inhibition and how their data “suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is reinvigorated on antibody treatment.”

In this excerpt from an interview he kindly gave BSB afterwards, he talks about the promise of cancer immunotherapy in lung cancer:

Tomorrow is the Thanksgiving holiday in the United States, so this will be the only post this week. Thanksgiving is a good time to take a moment out of the hectic life we all live to “smell the roses” and express gratitude for all the positive things around us.

Next week sees the start of the American Society of Hematology (ASH) annual meeting in San Francisco. The cancer conference circuit seems to roll quickly from one meeting to the next at the moment. There’s a lot of promising data, and while we can’t discuss the data before the meeting due to ASH embargo restrictions, next week we will be highlighting some of the presentations we are particularly looking forward to.

Happy Thanksgiving!

Subscribers can login below or you can purchase access to read more detail about all five Nature Letters, and their implications for the emerging field of immuno-oncology.

Overcoming or delaying resistance mechanisms or hitting multiple targets to greater effect will be achieved through combinations of drugs rather than single agent therapy. Combination strategies are the accepted future, whether drug companies like it or not.

In her keynote, Dr Jaffee also likened the revolution in immunotherapy to the same excitement the Beatles brought to music or the same magnitude of technology advances made by Apple. We agree completely.

“This is truly a brave new world of immunotherapy. I think the message is that the revolution is here, it’s ongoing, and it’s bursting out of melanoma into solid tumors.”

Interestingly, no immunotherapy data was considered to be of worthy of presentation in the plenary session at ASCO this year for the second year running, a decision that may reflect either an unwillingness to showcase early data, however good it may appear to be, or the influence of politics on the selection committee.

One potential combination is to target more than one checkpoint pathway to see if you can obtain a synergistic response. This is the rational for combining the monoclonal antibody ipilimumab and nivolumab. Ipilimumab (Yervoy) targets the CTLA-4 checkpoint protein that prevents dendritic cells from priming T cells to recognize tumors while nivolumab targets the PD-1 checkpoint protein that prevents T cells from attacking cancer cells. Yervoy is an FDA approved therapy for the treatment of metastatic melanoma.

Data published last year in The New England Journal of Medicine by Wolchok et al, showed that combining ‘ipi’ with ‘nivo’ gave more frequent and deeper responses in melanoma, but at the expense of much greater toxicity. Some 53% of patients receiving concurrent treatment had a grade 3-4 adverse event (see Table S-1B in the article).

Does it make sense to combine two immune pathway modulating agents? Does the enormous potential for synergy outweigh the additional toxicity?

To learn more about these insights, you can sign up below or subscribers can login for our analysis of the data on nivolumab in renal cell carcinoma (RCC) presented at ASCO 2014.